Mice were chronically infused with saline or nicotine (24 mg/kg/day) for 14 days. On day 15 mice received s.c. injection of PNU282987 (1, 3 and 9 mg/kg) or vehicle. Mice then were administered mecamylamine (2mg/kg; s.c.) 10 min prior to behavioral assessment of A) anxiety-like behaviors (Time spent in the open arm), B) somatic signs, and C) hyperalgesia (hot plate latency). Nicotine induced withdrawal symptoms: increased anxiety related behavior and somatic signs, but decreased hot plate latency. Compared to vehicle, pretreatment with PNU282987: A) attenuated the anxiety-like behavior at 9mg/kg; B) reduced somatic signs at 3 and 9mg/kg; and C) and no effect on hot plate latency in nicotine withdrawn mice. Each point represents the mean ± S.E.M. of n=6–8 mice per group. * Denotes p< 0.05 vs. Saline minipump group, # Denotes p< 0.05 vs. Nicotine minipump group. (MP) minipump. SV = Saline minipump/vehicle treatment; NV = Nicotine minipump/vehicle treatment; P28 = PNU282987 at 9 mg/kg.